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Molecular Mechanisms of CYP3A Gene Transactivations by Chemicals and their Species Differences
薬物によるCYP3A誘導の分子機序とその種差

Makoto OGINO, Kiyoshi NAGATA, Yasushi YAMAZOE
2000 Drug Metabolism and Pharmacokinetics  

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P450s belonging to the CYP3A subfamily constitute major forms in livers and intestines of hu man and experimental animals. Expressions of CYP3A forms are induced by treatment with many chemi cals, but their profiles differ among humans and experimental animals. Molecular mechanisms of CYP3A gene activation by chemicals had been little known until recently. A novel steroid hormone receptor, PXR (pregnane X receptor), has been isolated from mouse, rat, rabbit and human as a signal transduction
more » ... ec ule in CYP3A gene transactivation. Species differences observed on the induction profiles might be ex plained by the species specific response of their PXRs to chemicals. However, the diverse induction profiles of CYP3A forms are possible to be caused by interaction of PXR with transcription factors other than RXRα. In support with this idea, we have found that rat CYP3A1 gene is transactivated by an orphan nuclear recep tor, ARP-1 with PXR in the presence of inducers. To assess the induction potency of various chemicals for human CYP3A forms, further researches are necessary to clarify the transcriptional regulation of CYP3A forms.
doi:10.2133/dmpk.15.52 fatcat:2twln454mzenvjzextk6qzfgpi
Citation

Makoto OGINO, Kiyoshi NAGATA, Yasushi YAMAZOE. "Molecular Mechanisms of CYP3A Gene Transactivations by Chemicals and their Species Differences." Drug Metabolism and Pharmacokinetics 15.1 (2000) 52-56